Probing Cell Death Mechanisms with Small Molecules and Genomics Tools
Approach: The Stockwell lab sits at the
interface of chemistry and biology and is systematically using
small molecules to discover mechanisms underlying cellular
processes. Our approach is interdisciplinary, combining chemical
design and synthesis with genomics, biochemistry and cell biology,
with the ultimate goal of revealing new basic biological
mechanisms and disease pathophysiology.
We are using chemical and biological tools to study ferroptosis, a form of regulated cell death discovered in the Stockwell Lab. Ferroptosis is an iron-dependent form of oxidative, non-apoptotic cell death that is tightly linked to metabolism and disease.
We are exploring how ferroptosis in triggered during normal physiological processes and in disease states, and how it can be induced and inhibited for therapeutic benefit in various cancers and neurodegenerative diseases.
We use synthetic organic chemistry and computational chemistry tools to design chemical probes and drug candidates that reveal cellular and molecular mechanisms. We also use metabolomics, lipidomics, mass spectrometry imaging, CRISPR and siRNA/shRNA screening, protein expression and biochemistry, structure elucidation and animal models of disease to explore these questions.
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Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascon S, Hatzios SK, Kagan VE, Noel K, Jiang X, Linkermann A, Murphy ME, Overholtze M, Oyagi A, Pagnussat GC, Park J, Ran Q, Rosenfeld CS, Salnikow K, Tang D, Torti FM, Torti SV, Toyokuni S, Woerpel KA, Zhang DD Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease.
Cell 2017 Oct. [pubmed, pdf]